Genomic profile of appendiceal goblet cell carcinoid is distinct compared to appendiceal neuroendocrine tumor and conventional adenocarcinoma

Hum Pathol. 2018 Jul:77:166-174. doi: 10.1016/j.humpath.2018.03.026. Epub 2018 Apr 7.

Abstract

Goblet cell carcinoid (GCC) is a rare appendiceal tumor with unique morphologic features that shows glandular and neuroendocrine differentiation on immunohistochemistry. An additional component of adenocarcinoma (AC) can be present (GCC-AC). Both GCC and GCC-AC are staged and treated like AC. The histogenesis and genetic alterations underlying GCC and GCC-AC are unclear. Capture-based next-generation DNA sequencing targeting 479 cancer genes was performed on 19 appendiceal tumors: 4 GCC, 9 GCC-AC, 3 neuroendocrine tumors (NET), and 3 AC (2 conventional, 1 mucinous). Somatic coding mutations were not seen in any NET. Pathogenic (P)/likely pathogenic (LP) mutations were present in 1 GCC, 8 GCC-AC and all 3 AC cases. P/LP mutations in chromatin remodeling genes were seen in 4 (44.4%) GCC-AC cases, but not in NET, GCC or AC. In GCC-AC, P/LP mutations in ARID1A and RHOA were each present in 3 cases, and KDM6A and SOX9 mutations were each seen in 2 cases. APC and KRAS mutations were present in 1 conventional AC case, but were not observed in any GCC or GCC-AC. This limited series reveals mutations in SOX9, RHOA, and chromatin-modifier genes in goblet cell tumors, and shows that the mutational profile of GCC/GCC-AC is distinct from NET and conventional appendiceal AC.

Keywords: Adenocarcinoma; Appendix; Goblet cell carcinoid; Mutation; Next-generation sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Appendiceal Neoplasms / genetics*
  • Appendiceal Neoplasms / metabolism
  • Appendiceal Neoplasms / pathology
  • Carcinoid Tumor / genetics*
  • Carcinoid Tumor / metabolism
  • Carcinoid Tumor / pathology
  • Female
  • Genomics / methods
  • Goblet Cells / pathology
  • Humans
  • Intestinal Neoplasms / genetics*
  • Intestinal Neoplasms / metabolism
  • Intestinal Neoplasms / pathology
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / genetics*
  • Neuroendocrine Tumors / metabolism
  • Neuroendocrine Tumors / pathology
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology

Supplementary concepts

  • Gastro-enteropancreatic neuroendocrine tumor